Allergy and Heart Disease : Abstract Watch

Allergy and Heart Disease : Abstract Watch

Histamine–can it cause an acute coronary event?

Department of Cardiology, Jersey City Medical Center, Mount Sinai School of Medicine, New Jersey, USA.

Myocardial infarction (MI) occurring during the course of an allergic urticarial reaction in the absence of systemic hypotension has been rarely reported. This paper reports the case of a 28-year-old woman with no significant risk factors for coronary artery disease who presented with generalized urticaria associated with chest pain and had electrocardiographic and enzymatic evidence of an acute MI. Review of the literature suggests that local histamine release may induce spasm of the coronary vasculature, thus leading to myocardial ischemia and infarction.

Histamine, the main amine released during allergic reactions, can provoke coronary arterial spasm manifested as angina pectoris. This has been shown during clinical and laboratory studies. The effects of histamine on cardiac function are mediated via H1- and H2- receptors situated on the four cardiac chambers and coronary arteries. Coronary arteries of cardiac patients are hyperactive and contain stores of histamine which can initiate coronary artery spasm. Clinical observations indicate that angina pectoris or acute myocardial infarction can be provoked by acute allergic reaction. The coincidental occurrence of chest pain and allergic reaction accompanied by clinical and laboratory findings of classical angina pectoris seems to constitute the syndrome of allergic angina. The clinical symptoms of allergic angina include chest discomfort, dyspnoea, faintness, nausea, pruritus and urticaria. They are accompanied by signs such as hypotension, diaphoresis, pallor and bradycardia. There are also electrocardiographic findings indicating myocardial ischaemia, arrhythmias and conduction defects. Thus, in patients undergoing acute allergic reaction, the development of chest pain could be explained by the mechanism of coronary arterial spasm provoked by the release of histamine, which constitutes the syndrome of allergic angina.

Inflammatory mediators including histamine, neutral proteases, arachidonic acid products, platelet activating factor and a variety of cytokines and chemokines are increased in blood or urine in both allergic episodes and acute coronary syndromes. The release of mediators during allergic insults has been incriminated to induce coronary artery spasm and/or atheromatous plaque erosion or rupture. A common pathway between allergic and non-allergic coronary syndromes seems to exist. Today, there is evidence that mast cells not only enter the culprit region before plaque erosion or rupture but they release their contents before an actual coronary episode. Kounis syndrome is the concurrence of acute coronary syndromes with conditions associated with mast cell activation including allergic or hypersensitivity and anaphylactic or anaphylactoid insults. It is caused by inflammatory mediators released through mast cell activation. Kounis syndrome, as consequence, of the above pathophysiologic association is regarded as nature’s own experiment and magnificent natural paradigm showing novel way in an effort to prevent acute coronary syndromes. Drugs and natural molecules which stabilize mast cell membrane and monoclonal antibodies that protect mast cell surface could emerge as novel therapeutic modalities capable to prevent acute coronary and cerebrovascular events.

Hypersersensitivity and Kounis syndrome due to a viper bite.

A 60-year-old male was bitten by a venomous snake (Vipera ammodytes) and gradually developed signs of an allergic reaction including generalized itching, generalized rash, and chest discomfort. This was followed by severe retrosternal pain with electrocardiographic evidence of an inferior myocardial ischemia progressing to acute myocardial infarction. Cardiac enzymes and troponin, serum tryptase, and histamine were elevated. Coronary arteriography showed normal coronary arteries. This is a characteristic type I variant of Kounis syndrome, which is the concurrence of acute coronary syndromes with conditions associated with mast cell activation including allergic or hypersensitivity reactions as well as anaphylactic or anaphylactoid reactions. This is the first report to show that viper bites can induce allergic angina and/or allergic myocardial infarction.

Two cases of allergic angina and allergic myocardial infarction (Kounis syndrome) secondary to shellfish ingestion are described. The patients had pre-existing quiescent coronary artery disease (type II variant of the syndrome) and the allergic reaction following eating shellfish seemed to have triggered the development of an acute myocardial infarction. The clinical implications are also discussed.

During anaphylactic (or anaphylactoid) reactions severe cardiovascular events may occur, acute myocardial infarction among them. This etiology of myocardial infarction, is known, although it is infrequent and only sporadically reported in literature. A case of acute myocardial infarction secondary to anaphylactic reaction following shellfish ingestion, treated with subcutaneous epinephrine and in whom a rescue coronary angioplasty was necessary is reported. The mechanism of coronary occlusion in this kind of reaction and the possible influence on the efficacy of treatment is discussed.

The major risk of atherosclerotic disease is the occurrence of an acute coronary syndrome. The pathogenesis of instable angina involves the formation of an arterial thrombus as a consequence of the rupture of an atheromatous plaque. This risk of plaque rupture appears to depend on plaque morphology rather than plaque size or severity of stenosis. Ratio of lipid core to fibrous determined by the balance between smooth muscle cells proliferation and extracellular matrix synthesis stabilizing the plaque and macrophages which degrade collagen, determine the plaque vulnerability. The fibrous cap weakness leads to the plaque activation, plaque fissure or erosion activating a thrombotic cascade. A general inflammation or prothrombotic states are probably involved suggesting the need for a systemic therapeutic in addition with the treatment of the culprit lesion.

[Transmural myocardial infarction and Prinzmetal’s syndrome in an allergic reaction to glafenine. Physiopathological discussion. Apropos of a case]

The authors report the case of a 38 year old man who experienced at two month’ interval, hypersensitivity reactions to the ingestion of 200 mg tablets of glafenine, complicated on the first occasion by a transmural anterior wall myocardial infarction as the first manifestation of coronary artery disease and on the second occasion by Prinzmetal angina due to posterior wall ischaemia. Coronary angiography was more or less normal. The timing of the symptoms in the context of an anaphylactic reaction and their repetition when the same molecule was reintroduced are strong arguments in favour of the pathogenic role of glafenine, even in the absence of biological criteria which are always variable. The mechanism of the coronary problems is discussed with reference to mediators released during the anaphylactic reaction: coronary vasoconstriction due to histamine and leukotriene release; inhibition of prostaglandin synthesis causing potentiation of the effects of histamine; lowering of the vasodilatory and antiaggregant prostacyclin enhancing the vasoconstrictor and platelet aggregant action of thromboxane A2. All the conditions favouring the initiation of coronary spasm with eventual coronary thrombosis, the one aggravating the other, are therefore present.

The long QT syndrome is a rare disease. The prevalence is estimated at 1/5 000 to 1/20,000. Numerous drugs are contra-indicated because they can lengthen the QT interval. A case of pollen allergy in an adolescent with LQTS is described. The possibility to prescribe anti-H1 drugs is reviewed since cases of torsades de pointe and even deaths have been reported for terfenadine and astemizole. Diphenhydramine, orphenadrine and hydroxyzine are contra-indicated. No accidents and no effects on the QT interval have been published for ebastine, fexofenadine, desloratadine and levocetirizine. These anti-H1 drugs could be used with great care, without any association with drugs resulting in low serum potassium level. Azelastine eye drops have been authorized and a routine protection by inhaled corticosteroids

Heart problems reported with two non-sedating allergy drugs

Under certain circumstances, people taking either one of two non-sedating prescription antihistamines may develop life-threatening cardiac arrhythmias, commonly known as abnormal heart rhythms.

For this reason, FDA recently asked Marion Merrell Dow Inc., the manufacturer of Seldane (terfenadine), and Janssen Pharmaceutica, Inc., manufacturer of Hismanal (astemizole), to warn doctors and other health professionals of the problem.

Patients with liver disease are at increased risk from both drugs, because they cannot properly metabolize (process) them. This leads to a drug accumulation in the body that can result in arrhythmias and, in the case of Hismanal, other cardiovascular events, including cardiac arrest and death.

Taking excessive doses of either drug also increases these risks. With Hismanal, the majority of reported cardiovascular events have occurred in patients who greatly exceeded the recommended dose of 10 milligrams (one tablet) a day. However, arrhythmias have occurred at reported doses as low as 20 to 30 milligrams daily. It is important, therefore, that patients not exceed the recommended daily dose.

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Patients on Seldane are also at risk if they take the anti-fungal drug Nizoral (ketoconazole) or the antibiotic erythromycin (sold under several brand and genetic names) at the same time as Seldane. Studies have shown that Nizoral, also manufactured by Janssen, affects how the body metabolizes Seldane, increasing the blood levels of the allergy drug. Similar studies have not been conducted with erythromycin; however, arrhythmias have occurred in patients taking the antibiotic and Seldane at the same time.

Patients who experience fainting, dizziness or palpitations with either antihistamine should immediately discontinue use and consult their doctors for evaluation, which may include electrocardiographic (ECG) testing.

FDA has asked both companies to revise the physician labeling for these nonsedating antihistamines and develop patient leaflets that reflect the new warnings. FDA is working with Mation Merrell

Dow to plan further studies of Seldane metabolism and possible interactions with other drugs and to identify any other patient groups that may be at risk.

In addition, FDA is working with Janssen to warn against the use of Nizoral with Seldane.

COPYRIGHT 1992 U.S. Government Printing Office
COPYRIGHT 2004 Gale Group

I first became interested in the relationship between cardiac arrhymias and foods after hearing and reading papers by Dr. Solomon Klotz of Orlando, Florida. Dr. Klotz originally wrote on the connection between allergy and heart disease over 30 years ago, and about 14 years ago he updated his writings. Approximately 12 years ago, at the Illinois State Medical Society meeting, I presented a paper on cardiac arrhythmias due to foods and wrote a small chapter on the same subject for the textbook Clinical Ecology. In preparing these preparations, besides studying several patients intensively, I reviewed the literature on this topic, which turned out to be much more extensive and to go back farther than I had expected – back to the early 1900s, when clinicians first began to realize that there was a relationship.

In recent years there has been renewed interest in the role of allergy in heart disease. Several articles regarding the heart and its role in anaphylaxis have appeared in major journals; one study showed that patients in anaphylactic shock were often having allergic involvement of the heart muscle. Demonstration of the presence of mast cells (cells that contain the allergic mediators) tends to confirm the suspicion that the heart itself can be an allergic shock organ. It is now thought by some observers that the sustained hypotension or low blood pressure that may persist after anaphylaxis in some patients is actually due to allergic involvement of the heart and that this perhaps explains the rapid resolution brought about in some patients by anti-allergic measures. Of current interest is the possibility that allergy can induce spasms of coronary blood vessels and perhaps precipitate or contribute to the development of angina, or even mycardial infarction. At the very least, this association of allergy with heart disease explains or helps clarify some of the clinical observations that many physicians have made over the years.

Of current interest is the possibility that allergy can induce spasms of coronary blood vessels and perhaps precipitate or contribute to the development of angina, or even mycardial infarction. At the very least, this association of allergy with heart disease explains or helps clarify some of the clinical observations that many physicians have made over the years.For example, it has often been observed that food allergies can induce cardiac arrhythmias. (It is also thought that chemical and inhalant sensitivity can do the same. Freon propellants have long been suspected of inducing cardio toxicity and arrhythmias either in toxic doses or in regular doses in extremely sensitive persons, though this subject remains somewhat controversial.) Besides foods themselves, food additives, food preservatives, and other ingested chemicals can cause immunologic or non-immunologic responses. Among non-immunologic cardiac responses is food-aggravated gallbladder or esophageal disease, particularly hiatus hernia, which can induce vagovagal reflexes that occasionally cause arrhythmias.

Suspect foods may cause symptoms or potential cardiac symptoms within minutes of their ingestion or, and this is the cause for confusion, the symptoms can be delayed for hours. Perhaps for this reason, the Holter Monitor, a portable device used to continuously monitor cardiac rate and rhythm, is rarely used to detect cardiac arrhythmias due to foods. Nevertheless, this diagnosis is suggested in any patient who is having and cardiac manifestation and who can be demonstrated to be allergic (though non-immunologic mechanisms may also contribute). Sometimes confirmation can be made by challenge feeding and testing or by provocative testing, but most often it is done by suspicion, perhaps on the basis of testing (blood tests), leading to elimination diets with either improvement or lack of improvement.

For me, the exciting part of this saga is the growing awareness in the rest of the field of allergy, and perhaps internal medicine and cardiology as well, that allergic factors may be significant in some cardiac patients, that the heart itself is a shock organ, and that coronary artery spasm, long suspected of contributing to angina or even myocardial infarction, may be triggered by allergy.In other words, if a patient shows strongly allergic to wheat and milk on blood or skin provocative tests and then eliminates these foods from his or her diet for a period of weeks or months with an improvement of cardiac status, the diagnosis is suggested, but it is of course still presumptive. To be really scientific, one would have to double blind the study by adding the food back without the patient or the investigator knowing, to see whether symptoms would eventually recur, obviously a difficult, if not impossible, procedure. Also, such double-blind, crossover studies are difficult in food allergy because avoidance for a period of time leads to a loss of intolerance, and therefore rechallenge takes a while before sensitivity again develops.

For me, the exciting part of this saga is the growing awareness in the rest of the field of allergy, and perhaps internal medicine and cardiology as well, that allergic factors may be significant in some cardiac patients, that the heart itself is a shock organ, and that coronary artery spasm, long suspected of contributing to angina or even myocardial infarction, may be triggered by allergy.

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